Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

Miniature tunable Airy beam optical meta-device

Tunable Airy beams with controllable propagation trajectories have sparked interest in various fields,such as optical manipulation and laser fabrication.Existing research approaches encounter challenges related to insufficient compactness and integration feasibility,or they require enhanced tunability to enable real-time dynamic manipulation of the propagation trajectory.In this work,we present a novel method that utilizes a dual metasurface system to surpass these limitations,significantly enhancing the practical potential of the Airy beam.Our approach involves encoding a cubic phase profile and two off-axis Fresnel lens phase profiles across the two metasurfaces.The validity of the proposed strategy has been confirmed through simulation and experimental results.The proposed meta-device addresses the existing limitations and lays the foundation for broadening the applicability of Airy beams across diverse domains,encompassing light-sheet microscopy,laser fabrication,optical tweezers,etc.

Light-based 3D printing of stimulus-responsive hydrogels forminiature devices:recent progress and perspective

Miniature devices comprising stimulus-responsive hydrogels with high environmental adaptability are now considered competitive candidates in the fields of biomedicine,precise sensors,and tunable optics.Reliable and advanced fabricationmethods are critical formaximizing the application capabilities ofminiature devices.Light-based three-dimensional(3D)printing technology offers the advantages of a wide range of applicable materials,high processing accuracy,and strong 3D fabrication capability,which is suitable for the development of miniature devices with various functions.This paper summarizes and highlights the recent advances in light-based 3D-printed miniaturized devices,with a focus on the latest breakthroughs in lightbased fabrication technologies,smart stimulus-responsive hydrogels,and tunable miniature devices for the fields of miniature cargo manipulation,targeted drug and cell delivery,active scaffolds,environmental sensing,and optical imaging.Finally,the challenges in the transition of tunable miniaturized devices from the laboratory to practical engineering applications are presented.Future opportunities that will promote the development of tunable microdevices are elaborated,contributing to their improved understanding of these miniature devices and further realizing their practical applications in various fields.

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs

Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group(n=3)and a non-susceptible group(n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.

Miniaturized power detection module operating in millimeter wave band

The miniaturized broadband detection module can be embedded into the microwave application system such as the front end of the transmitter to detect the power or other parameters in real time.It is highly prospective in military and scientific research.In this paper,a broadband power detection module operating at 26.5 GHz-40.0 GHz is designed by using low-barrier Schottky diode as the detector and a comparator for threshold output.This module can dynamically detect the power range between-10 dBm and 10 dBm with the detection accuracy of 0.1 dB.Further,the temperature compensation circuit is also applied to improve the measurement error.As a result,the resulted error low to±1 dB in the temperature range of -55℃ to +85℃ is achieved.The designed module is encapsulated by a Kovar alloy with a small volume of 9 mm×6 mm×3 mm.This endows the designed module the advantages of small size,easy integration,and low cost,and even it is applicable to high-reliability environments such as satellites.

Identifying the enhancement mechanism of Al/MoO_(3) reactive multilayered films on the ignition ability of semiconductor bridge using a one-dimensional gas-solid two-phase flow model

Energetic Semiconductor bridge(ESCB)based on reactive multilayered films(RMFs)has a promising application in the miniature and intelligence of initiator and pyrotechnics device.Understanding the ignition enhancement mechanism of RMFs on semiconductor bridge(SCB)during the ignition process is crucial for the engineering and practical application of advanced initiator and pyrotechnics devices.In this study,a one-dimensional(1D)gas-solid two-phase flow ignition model was established to study the ignition process of ESCB to charge particles based on the reactivity of Al/MoO_(3) RMFs.In order to fully consider the coupled exothermic between the RMFs and the SCB plasma during the ignition process,the heat release of chemical reaction in RMFs was used as an internal heat source in this model.It is found that the exothermal reaction in RMFs improved the ignition performance of SCB.In the process of plasma rapid condensation with heat release,the product of RMFs enhanced the heat transfer process between the gas phase and the solid charge particle,which accelerated the expansion of hot plasma,and heated the solid charge particle as well as gas phase region with low temperature.In addition,it made up for pressure loss in the gas phase.During the plasma dissipation process,the exothermal chemical reaction in RMFs acted as the main heating source to heat the charge particle,making the surface temperature of the charge particle,gas pressure,and gas temperature rise continuously.This result may yield significant advantages in providing a universal ignition model for miniaturized ignition devices.

Current Situation and Progress of Pig Model in Otology Research

Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. This article introduces the applications, current status, progress, advantages, and issues of using pigs as otologic animal models. It summarizes current research on pigs in the fields of hearing disorders, otitis, vertigo, cochlea, gene editing, and tissue engineering, among other otologic and audiological areas. These models are valuable for translating basic medical science into clinical applications. Based on this, platforms have been established for studying deafness and vertigo, cochlear implantation experiments, stem cell and gene therapy, and tissue engineering. These serve as ideal experimental models for the prevention and treatment of ear diseases, pointing toward new directions. This will bolster the promotion and application of pig models in the fields of tissue engineering and gene editing in the future.

An AuNPs/Mesoporous NiO/Nickel Foam Nanocomposite as a Miniaturized Electrode for Heavy Metal Detection in Groundwater

Heavy metals,notably Pb2+and Cu^(2+),are some of the most persistent contaminants found in groundwater.Frequent monitoring of these metals,which relies on efficient,sensitive,cost-effective,and reliable methods,is a necessity.We present a nanocomposite-based miniaturized electrode for the concurrent measurement of Pb2+and Cu^(2+)by exploiting the electroanalytical technique of square wave voltammetry.We also propose a facile in situ hydrothermal calcination method to directly grow binder-free mesoporous Ni O on a three-dimensional nickel foam,which is then electrochemically seeded with gold nanoparticles(Au NPs).The meticulous design of a low-barrier Ohmic contact between mesoporous Ni O and Au NPs facilitates target-mediated nanochannel-confined electron transfer within mesoporous Ni O.As a result,the heavy metals Pb2+(0.020 mg.L^(-1)detection limit;2.0–16.0 mg.L^(-1)detection range)and Cu^(2+)(0.013 mg.L^(-1)detection limit;0.4–12.8 mg.L^(-1)detection range)can be detected simultaneously with high precision.Furthermore,other heavy metal ions and common interfering ions found in groundwater showed negligible impacts on the electrode’s performance,and the recovery rate of groundwater samples varied between 96.3%±2.1%and 109.4%±0.6%.The compactness,flexible shape,low power consumption,and ability to remotely operate our electrode pave the way for onsite detection of heavy metals in groundwater,thereby demonstrating the potential to revolutionize the field of environmental monitoring.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Smart palm-size optofluidic hematology analyzer for automated imaging-based leukocyte concentration detection

A critical function of flow cytometry is to count the concentration of blood cells,which helps in the diagnosis of certain diseases.However,the bulky nature of commercial flow cytometers makes such tests only available in hospitals or laboratories,hindering the spread of point-of-care testing(POCT),especially in underdeveloped areas.Here,we propose a smart Palm-size Optofluidic Hematology Analyzer based on a miniature fluorescence microscope and a microfluidic platform to lighten the device to improve its portability.This gadget has a dimension of 35×30×80 mm and a mass of 39 g,less than 5%of the weight of commercially available flow cytometers.Additionally,automatic leukocyte concentration detection has been realized through the integration of image processing and leukocyte counting algorithms.We compared the leukocyte concentration measurement between our approach and a hemocytometer using the Passing-Bablok analysis and achieved a correlation coefficient of 0.979.Through Bland-Altman analysis,we obtained the relationship between their differences and mean measurement values and established 95%limits of agreement,ranging from−0.93×10^(3)to 0.94×10^(3)cells/μL.We anticipate that this device can be used widely for monitoring and treating diseases such as HIV and tumors beyond hospitals.

Transcriptomic and proteomic studies of condylar ossification of the temporomandibular joint in porcine embryos

Background:The ossification mechanism of the temporomandibular joint(TMJ)condyle remains unclear in human embryo.The size and structure of TMJ,shape of articular disc and the characteristics of omnivorous chewing in the pig are similar to those of humans.The pig is an ideal animal for studying the mechanism of ossification of the TMJ condyle during the embryonic period.Method:In a previous study by our group,it was found that there was no condylar ossification on embryonic day(E)45,but the ossification of condyle occurred between E75 and E90.In this study,a total of 12 miniature pig embryos on E45 and E85 were used.Six embryos were used for tissue sections(3 in each group).The remaining six embryos were used for transcriptomic and proteomic studies to find differential genes and proteins.The differentially expressed genes in transcriptome and proteomic analysis were verified by QPCR.Results:In total,1592 differential genes comprising 1086 up-regulated genes and 506 down-regulated genes were screened for fold changes of≥2 to≤0.5 between E45 and E85.In the total of 4613 proteins detected by proteomic analysis,there were 419 differential proteins including 313 up-regulated proteins and 106 down-regulated proteins screened for fold changes of≥2 to≤0.5 between E45 and E85.A total of 36 differential genes differing in both transcriptome and proteome analysis were found.QPCR analysis showed that 14 of 15 selected genes were consistent with transcriptome analysis.Conclusion:Condylar transcriptome and proteomic analysis during the development of TMJ in miniature pigs revealed the regulatory genes/proteins of condylar ossification.

A compact and closed-loop spin-exchange relaxation-free atomic magnetometer for wearable magnetoencephalography

Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer with compact size and good performance is crucial to the new generation of wearable magnetoencephalography(MEG)system.In this paper,we developed a compact and closed-loop SERF magnetometer with the dimensions of 15.0×22.0×30.0 mm^(3)based on a single-beam configuration.The bandwidth of the magnetometer was extended to 675 Hz while the sensitivity was maintained at 22 f T/Hz^(1/2).A nearly 3-fold enhancement of the bandwidth was obtained in comparison with the open-loop control.The implementation of the closed-loop control also greatly improved the dynamic range,enabling the magnetometer to be robust against the disturbance of the ambient field.Moreover,the magnetometer was successfully applied for the detection of humanα-rhythm and auditory evoked fields(AEFs),which demonstrated the potential to be extended to multi-channel MEG measurements for future neuroscience studies.

Surface reconstruction,modification and functionalization of natural diatomites for miniaturization of shaped heterogeneous catalysts

Since the discovery of mesoporous silica in 1990s,there have been numerous mesoporous silica-based nanomaterials developed for catalytic applications,aiming at enhanced catalytic activity and stability.Recently,there have also been considerable interests in endowing them with hierarchical porosities to overcome the diffusional limitation for those with long unimodal channels.Present processes of making mesoporous silica largely rely on chemical sources which are relatively expensive and impose environmental concerns on their processes.In this regard,it is desirable to develop hierarchical silica supports from natural minerals.Herein,we present a series of work on surface reconstruction,modification,and functionalization to produce diatomite-based catalysts with original morphology and macro-meso-micro porosities and to test their suitability as catalyst supports for both liquid-and gas-phase reactions.Two wet-chemical routes were developed to introduce mesoporosity to both amorphous and crystalline diatomites.Importantly,we have used computational modeling to affirm that the diatomite morphology can improve catalytic performance based on fluid dynamics simulations.Thus,one could obtain this type of catalysts from numerous natural diatoms that have inherently intricate morphologies and shapes in micrometer scale.In principle,such catalytic nanocomposites acting as miniaturized industrial catalysts could be employed in microfluidic reactors for process intensification.

Whole-genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs

Background:Hundreds of single-nucleotide polymorphism(SNP)sites have been found to be potential genetic markers of type 2 diabetes mellitus(T2DM).However,SNPs related to T2DM in minipigs have been less reported.This study aimed to screen the T2DM-susceptible candidate SNP loci in Bama minipigs so as to improve the success rate of the minipig T2DM model.Methods:The genomic DNAs of three Bama minipigs with T2DM,six sibling lowsusceptibility minipigs with T2DM,and three normal control minipigs were compared by whole-genome sequencing.The T2DM Bama minipig-specific loci were obtained,and their functions were annotated.Meanwhile,the Biomart software was used to perform homology alignment with T2DM-related loci obtained from the human genome-wide association study to screen candidate SNP markers for T2DM in Bama miniature pigs.Results:Whole-genome resequencing detected 6960 specific loci in the minipigs with T2DM,and 13 loci corresponding to 9 diabetes-related genes were selected.Further,a set of 122 specific loci in 69 orthologous genes of human T2DM candidate genes were obtained in the pigs.Collectively,a batch of T2DM-susceptible candidate SNP markers in Bama minipigs,covering 16 genes and 135 loci,was established.Conclusions:Whole-genome sequencing and comparative genomics analysis of the orthologous genes in pigs that corresponded to the human T2DM-related variant loci successfully screened out T2DM-susceptible candidate markers in Bama miniature pigs.Using these loci to predict the susceptibility of the pigs before constructing an animal model of T2DM may help to establish an ideal animal model.

Cloning and Sequence Analysis on cDNA of Growth Hormone Releasing Hormone Receptor Gene from Wuzhishan Miniature Pig

[Objective] cDNA of growth hormone releasing hormone （GHRH） receptor gene from Wuzhishan miniature pig was cloned and its sequence was also analyzed. [Method] Using genomic DNA extracted from porcine ear tissues of Wuzhishan miniature pig as the template, three pairs of primers were designed by the reported cDNA sequence of porcine GHRH, and cDNA was also amplified by RT-PCR. After being recovered and purified, PCR products were ligated to pMD18-T and then transformed into Escherichia coli DH5a. The transformation products were analyzed by PCR and double enzyme digestion to screen positive clones, and the positive clones were sequenced after identification in LB liquid medium. [ Result] cDNA of Wuzhishan miniature pig GHRH receptor gene was obtained successfully, and its length was 1 577 bp coding 423 amino acids. BLAST analysis showed that there were only 23 nuoleotides in difference between this fragment and pomine GHRH receptor gene, and its homology was 98%. However, both GHRH receptor genes were constituted by 423 amino acids with the sequence homology of 96%. [ Conclusion] This study provides theoretical basis for further studies on the dwarf mechanism of Wuzhishan miniature pig.

TECA hybrid artificial liver support system in treatment of acute liver failure

AIM: To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF). METHODS: The porcine liver cells (1-2) x 10(10) were separated from the Chinese small swine and cultured in the bioreactor of TECA-BALSS at 37.0 degrees C and circulated through the outer space of the hollow fiber tubes in BALSS. The six liver failure patients with various degree of hepatic coma were treated by TECA-HALSS and with conventional medicines. The venous plasma of the patients was separated by a plasma separator and treated by charcoal adsorbent or plasma exchange. The plasma circulated through the inner space of the hollow fiber tubes of BALSS and mixed with the patients' blood cells and flew back to their blood circulation. Some small molecular weight substances were exchanged between the plasma and porcine liver cells. Each treatment lasted 6.0-7.0 h. Physiological and biochemical parameters were measured before,during and after the treatment. RESULTS: The average of porcine liver cells was (1.0-3.0) x 10(10) obtained from each swine liver using our modified enzymatic digestion method. The survival rate of the cells was 85%-93% by trypan blue stain and AO/PI fluorescent stain. After cultured in TECA-BALSS bioreactor for 6 h, the survival rate of cells still remained 70%-85%. At the end of TECA-HALSS treatment, the levels of plasma NH(3), ALT, TB and DB were significantly decreased. The patients who were in the state of drowsiness or coma before the treatment improved their appetite significantly and regained consciousness, some patients resumed light physical work on a short period after the treatment.One to two days after the treatment, the ratio of PTA increased warkedly. During the treatment, the heart rates, blood pressure, respiration condition and serum electrolytes (K(+), Na(+) and Cl(-)) were stable without thrombosis and bleeding in all the six patients. CONCLUSION: TECA-HALSS treatment could be a rapid, safe and efficacious method to provide temporary liver support for patients with ALF.

Cloning and cDNA Sequence Analysis of SLA-DQA Gene from Hainan Wuzhishan Miniature Pig

[ Objective] The study aimed to lay a foundation for studying immune recognition mechanism in xenotransplantation. [ Method] SLA- DQA gene of Hainan Wuzhishan miniature pig was cloned by RT-PCR and sequenced. J-Result] The SLA-DQA gene sequence of Wuzhishan minia- ture pig contained 768 nucleotides, among which 1 -765 were the complete open reading frame, encoding 255 amino acids. SLA-DQA cDNA se- quence and its deduced amino acid sequence of Wuzhishan miniature pig were most similar to those of the other miniature pigs in China. When compared with corresponding cDNA sequences and the amino acid sequences in other species, the homology with human was obviously higher than that with mouse. [ Conclusion] As the Chinese pig breed suitable for xenotransplantation, Wuzhishan miniature pig has significant importance to ser- ial studies on immunogenetics characteristics.

Retrograde intrarenal surgery vs miniaturized percutaneous nephrolithotomy to treat lower pole renal stones 1.5-2.5 cm in diameter

AIM To compare the outcomes of retrograde intrarenal surgery(RIRS) and miniaturized percutaneous nephrolithotomy(mini-PCNL) in treating lower pole(LP) renal stones with a diameter of 1.5-2.5 cm.METHODS A total of 216 patients who underwent mini-PCNL(n = 103) or RIRS n = 113) for LP stones with a diameter of 1.5-2.5 cm were enrolled between December 2015 and April 2017 at the Urology Department of Ningbo Urology and Nephrology Hospital.RESULTS Significant differences were found in the hospital stay(9.39 ± 4.01 vs 14.08 ± 5.26, P < 0.0001) and hospitalization costs(2624.5 ± 513.36 vs 3255.2 ± 976.5, P < 0.0001) between the RIRS and mini-PCNL groups. The mean operation time was not significantly different between the RIRS group(56.48 ± 24.77) and the mini-PCNL group(60.04 ± 30.38, P = 0.345). The stone-free rates at the first postoperative day(RIRS vs mini-PCNL: 90.2% vs 93.2%, P = 0.822) and the second month postoperatively(RIRS vs mini-PCNL: 93.8% vs 95.1%, P = 0.986) were not significantly different.CONCLUSION RIRS and mini-PCNL are both safe and effective methods for treating LP stones with a diameter of 1.5-2.5 cm. RIRS can be considered as an alternative to PCNL for the treatment for LP stones of 1.5-2.5 cm.

Heat Stress Upregulates the Expression of TLR4 and Its Alternative Splicing Variant in Bama Miniature Pigs

Alternative splicing is a cellular mechanism in eukaryotes that results in considerable diversity ofgene products. It plays an important role in several diseases and cellular signal regulation. Heat stress is a major factor that induces immunosuppression in pigs. Little is known about the correlation between alternative splicing and heat stress in pigs. Therefore, this study aimed to clone, sequence and quantify the alternative splicing variant of toll-like receptor 4 （TLR4） in Bama miniature pigs （Sus scrofa domestica） following exposure to heat stress. The results showed that the second exon of TLR4 was spliced and 167 bp shorter in the alternative splicing variant, and the protein was putatively identified as a type of truncated membrane protein consisting of extramembrane, transmembrane and intramembrane regions lacking a signal peptide. Further, it was not a non- classical secretory protein. Five potential reference genes were screened for their potential as reliable standards to quantify the expression of TLR4 alternative spliced variants by real-time quantitative reverse-transcriptase polymerase chain reaction （qRT-PCR）. The stability of these reference genes was ranked using the geNorm and NormFinder programs, and ribosomal protein L4 （RPL4） and TATA box-binding protein （TBP） were found to be the two genes showing the most stable expression in the in vitro cultured peripheral blood mononuclear ceils （PBMCs） during heat shock. The mRNA level of the TLR4 gene （both classical and spliced） in stressed pigs increased significantly （P〈0.05）. Further, the expression levels of the alternative spliced variant of TLR4 （TLR4-ASV） showed a 2-3 folds increase in heat-stressed PBMCs as compared to control pigs. The results of the present study suggested that heat shock might modulate the host immune response by regulating the expressions of TLR4 and its alternative splicing variant.

Oncogenic activity of MCM7 transforming cluster

The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.